2.1 Dendritic Cell Immunotherapy
There is great interest in developing effective autologous immunotherapeutic vaccines for treating or preventing human cancer. Success at such autologous immunotherapy requires the development of a vaccine that is both specific for the patient's cancer and capable of eliciting a potent immune response.
Autologous dendritic cell therapy is an approach that involves priming a patient's immune system to attack the patient's cancer cells. In this procedure, certain immune cells, namely dendritic cells (DCs), are exposed to, or “pulsed” with, cancer cells comprising the patient's specific cancer antigens. The dendritic cells pulsed with specific cancer antigens then present these antigens to naïve T lymphocytes of the immune system. This leads to the priming of the T lymphocytes into a population of effector T lymphocytes, which attack cancer cells in the patient's body presenting those antigens.
To produce an autologous dendritic cell cancer vaccine, monocytes are collected from a cancer patient by leukapheresis. The monocytes are then differentiated in vitro into DCs, which are then pulsed with cancer cells related to the type of cancer being treated, and re-administrated to the patient to elicit an immune response against its cancer.
2.2 Cell Death
Cell death can be broadly classified into two types: necrosis and apoptosis. Necrosis is cell death caused by external factors damaging cells or tissue, whereas apoptosis is a programmed cell death which occurs naturally in living organisms. Cell death through either necrosis or apoptosis can be immunogenic or non-immunogenic. A specific type of apoptosis, characterized as immunogenic cell death (ICD), has been identified as being capable of inducing a robust immunogenic response. (G. Kroemer et al., 2013, Immunogenic Cell Death in Cancer therapy. Ann. Rev. Immunol., vol 31, pp. 51-72). Cells undergoing ICD are preferentially recognized by DCs, and can be used to pulse DCs, which, in turn, expose antigen from these dying cells to the immune system.
Despite the recent advances in the field of immunotherapy, the challenge of standardizing a process for producing an autologous cancer vaccine while ensuring optimal and reproducible antigen presentation by DCs after pulsing with cancer cells remains unmet.